Poor adherence to highly active antiretroviral therapy (HAART) is a significant clinical issue in the treatment and prevention of HIV, as extremely high levels of HAART adherence are necessary to maintain viral suppression. Recent evidence suggests only 19% of individuals on HAART nationwide show optimal adherence and achieve full viral suppression. Efforts to better understand and improve HAART adherence are crucial to managing the HIV/AIDS epidemic. A group that evidences a disproportionate burden of new HIV infection is low-income minority substance users living in urban areas. In D.C. specifically, where the highest rate of new HIV/AIDS cases in the U.S. are reported each year, the most notable increase in new infection has been among low-income, minority substance users. In this group, one of the most significant and prevalent patient-level barriers to adherence is depressive symptoms. Depressive symptoms, even at subclinical levels, predict nonadherence above and beyond other relevant psychosocial factors, including current substance use. Despite the focus on depressive symptoms as a reliable and powerful predictor of HAART nonadherence among substance users with HIV, few studies have sought to test potential mechanisms underlying this relationship, which is an important step to advance our understanding of how depression affects adherence to inform intervention efforts in this group. Using reinforcement-based theory, we focus on two key shared behavioral/environmental factors related to both depression and substance use that include: (1) reductions in goal-directed activity level and (2) reductions in positive reinforcement in one's environment. Extensive evidence suggests the relevance of these factors to HAART adherence; however, they have not been tested as potential mediators of the relationship between depressive symptoms and HAART adherence. Thus, the aim of the proposal is to test the mediating roles of goal-directed activity level and positive reinforcement in this relationship in a sample of low-income HIV positive substance users. We will use a repeated measures design assessing self-report and clinician rated measures of depressive symptoms, substance use, goal-directed activity level, positive reinforcement, and HAART adherence, as well as clinical indicators (Viral Load, CD4 count) over a 3-month period. The sample will include 125 HIV positive substance users recruited from a large HIV clinic in Washington, D.C. Results have important implications as they would provide the first test of potential mechanisms that may account for the relationship between depression and HAART adherence among low-income, minority substance users, a group at extremely high-risk for poor HIV outcomes. As Kazdin (2007) noted, it is crucial to identify mediators in order to maximize parsimony and optimize efficacy of interventions. Current findings have clear implications for increasing effectiveness and parsimony of integrated interventions to target depression and HAART adherence, as well as important implications for prevention, as better understanding and improving adherence may reduce the risk of transmission in this high-risk group. PUBLIC HEALTH RELEVANCE: Efforts to better understand and improve adherence to highly active antiretroviral therapy (HAART) among low- income, minority substance users living with HIV is crucial to managing the HIV/AIDS epidemic. One reliable and powerful predictor of nonadherence in this population is depression, yet to date no studies have tested how depression impacts adherence. The goal of the current proposal is to test potential mechanisms of the relationship between depression and HAART nonadherence among low-income HIV positive substance users, which has clear implications for increasing effectiveness and parsimony of existing prevention and treatment interventions.